tbuckley/cabot-search huggingface dataset:
Correction: Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC: biomarker analysis from a single-arm, phase 2 trial
Journal: Journal for ImmunoTherapy of Cancer (2023)

Correction: Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC
Uninformed Consent
Authors: Katherine A. Stafford
Journal: Annals of Internal Medicine (2023)

On Being a DoctorJuly 2023Uninformed ConsentKatherine A. Stafford, MBBS, MPHKatherine A. Stafford, MBBS, MPHDenver Health and Hospital Authority, University of Colorado School of Medicine, Denver, ColoradoSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-0569 Audio Reading - “Uninformed Consent” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Uninformed Consent” by Katherine A. Stafford, MBBS, MPH Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail At the beginning of my intern year in internal medicine, I remember scurrying behind my first resident while learning to do admissions. After asking the patient a battery of questions, she would conclude, “Do you want to be full code? That means doing everything possible to save your life if needed.”For months, I barely gave this part of the encounter any thought. I noticed that every physician had a slightly different way of asking code status but that it was always done hurriedly, right before leaving the room, and often with a twinge of guilt. Although I poured my ... Author, Article, and Disclosure InformationAuthors: Katherine A. Stafford, MBBS, MPHAffiliations: Denver Health and Hospital Authority, University of Colorado School of Medicine, Denver, ColoradoCorresponding Author: Katherine A. Stafford, MBBS, MPH, Denver Health and Hospital Authority, 777 Bannock Street, Denver, CO 80204; e-mail, katherine.stafford@cuanschutz.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Uninformed Consent” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Uninformed Consent” by Katherine A. Stafford, MBBS, MPH Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics July 2023Volume 176, Issue 7Page: 1005-1006 ePublished: 18 July 2023 Issue Published: July 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cardiovascular morbidity and mortality in patients in Wales, UK with resistance to thyroid hormone β (RTHβ): a linked-record cohort study
Authors: Onyebuchi E Okosieme, Danyal Usman, Peter N Taylor, Colin M Dayan, Greta Lyons, Carla Moran, Krishna Chatterjee, Dafydd Aled Rees
Journal: The Lancet Diabetes & Endocrinology (2023)
Potent broadly neutralizing antibody VIR-3434 controls hepatitis B and D virus infection and reduces HBsAg in humanized mice
Authors: Florian A. Lempp, Tassilo Volz, Elisabetta Cameroni, Fabio Benigni, Jiayi Zhou, Laura E. Rosen, Julia Noack, Fabrizia Zatta, Hannah Kaiser, Siro Bianchi, Gloria Lombardo, Stefano Jaconi, Lucia Vincenzetti, Hasan Imam, Leah B. Soriaga, Nadia Passini, David M. Belnap, Andreas Schulze, Marc Lütgehetmann, Amalio Telenti, Andrea L. Cathcart, Gyorgy Snell, Lisa A. Purcell, Christy M. Hebner, Stephan Urban, Maura Dandri, Davide Corti, Michael A. Schmid
Journal: Journal of Hepatology (2023)

Chronic hepatitis B is a global public health problem, and coinfection with hepatitis delta virus (HDV) worsens disease outcome. Here, we describe a hepatitis B virus (HBV) surface antigen (HBsAg)-targeting monoclonal antibody (mAb) with the potential to treat chronic hepatitis B and chronic hepatitis D.HBsAg-specific mAbs were isolated from memory B cells of HBV vaccinated individuals. In vitro neutralization was determined against HBV and HDV enveloped with HBsAg representing eight HBV genotypes. Human liver-chimeric mice were treated twice weekly with a candidate mAb starting 3 weeks post HBV inoculation (spreading phase) or during stable HBV or HBV/HDV coinfection (chronic phase).From a panel of human anti-HBs mAbs, VIR-3434 was selected and engineered for pre-clinical development. VIR-3434 targets a conserved, conformational epitope within the antigenic loop of HBsAg and neutralized HBV and HDV infection with higher potency than hepatitis B immunoglobulins in vitro. Neutralization was pan-genotypic against strains representative of HBV genotypes A-H. In the spreading phase of HBV infection in human liver-chimeric mice, a parental mAb of VIR-3434 (HBC34) prevented HBV dissemination and the increase in intrahepatic HBV RNA and covalently closed circular DNA. In the chronic phase of HBV infection or co-infection with HDV, HBC34 treatment decreased circulating HBsAg by >1 log and HDV RNA by >2 logs.The potently neutralizing anti-HBs mAb VIR-3434 reduces circulating HBsAg and HBV/HDV viremia in human liver-chimeric mice. VIR-3434 is currently in clinical development for treatment of patients with chronic hepatitis B or D.Chronic infection with hepatitis B virus and co-infection with hepatitis D virus place approximately 290 million individuals worldwide at risk of severe liver disease and cancer. Available treatments result in low rates of functional cure or require lifelong therapy that does not eliminate the risk of liver disease. We isolated and characterized a potent human antibody that neutralizes hepatitis B and D viruses and reduces infection in a mouse model. This antibody could provide a new treatment for patients with chronic hepatitis B and D.
Prevalence and Associations of Nonglaucomatous Optic Nerve Atrophy in High Myopia
Authors: Mukharram M. Bikbov, Ellina M. Iakupova, Timur R. Gilmanshin, Guzel M. Bikbova, Gyulli M. Kazakbaeva, Songhomitra Panda-Jonas, Leisan I. Gilemzianova, Jost B. Jonas
Journal: Ophthalmology (2023)
Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study
Authors: Leonard B. Saltz, Stephen Clarke, Eduardo Díaz-Rubio, Werner Scheithauer, Arie Figer, Ralph Wong, Sheryl Koski, Mikhail Lichinitser, Tsai-Shen Yang, Fernando Rivera, Felix Couture, Florin Sirzén, Jim Cassidy
Journal: Journal of Clinical Oncology (2023)

To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).
Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200
Authors: Bruce J. Giantonio, Paul J. Catalano, Neal J. Meropol, Peter J. O'Dwyer, Edith P. Mitchell, Steven R. Alberts, Michael A. Schwartz, Al B. Benson
Journal: Journal of Clinical Oncology (2023)

Purpose Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer. Patients and Methods Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity. Results The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P &lt; .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively ( P &lt; .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting. Conclusion The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal cancer.
Mpox vaccine and infection-driven human immune signatures: an immunological analysis of an observational study
Authors: Hallie Cohn, Nathaniel Bloom, Gianna Y Cai, Jordan J Clark, Alison Tarke, Maria C Bermúdez-González, Deena R Altman, Luz Amarilis Lugo, Francisco Pereira Lobo, Susanna Marquez, Jin-Qiu Chen, Wenlin Ren, Lili Qin, Jennifer L Yates, Danielle T Hunt, William T Lee, Shane Crotty, Florian Krammer, Alba Grifoni, Alessandro Sette, Viviana Simon, Camila H Coelho
Journal: The Lancet Infectious Diseases (2023)
Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations
Authors: Matteo Parotto, Mariann Gyöngyösi, Kathryn Howe, Sheila N Myatra, Otavio Ranzani, Manu Shankar-Hari, Margaret S Herridge
Journal: The Lancet Respiratory Medicine (2023)

Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after the acute phase, lasting for weeks or months after the initial acute illness. The post-acute sequelae of COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID or post-COVID-19 condition. The substantial burden of this multisystem condition is felt at individual, health-care system, and socioeconomic levels, on an unprecedented scale. Survivors of COVID-19-related critical illness are at risk of the well known sequelae of acute respiratory distress syndrome, sepsis, and chronic critical illness, and these multidimensional morbidities might be difficult to differentiate from the specific effects of SARS-CoV-2 and COVID-19. We provide an overview of the manifestations of post-COVID-19 condition after critical illness in adults. We explore the effects on various organ systems, describe potential pathophysiological mechanisms, and consider the challenges of providing clinical care and support for survivors of critical illness with multisystem manifestations. Research is needed to reduce the incidence of post-acute sequelae of COVID-19-related critical illness and to optimise therapeutic and rehabilitative care and support for patients.
Correction: Cell autonomous expression of BCL6 is required to maintain lineage identity of mouse CCR6+ ILC3s
Authors: Yuling Li, Jing Ge, Xiaohong Zhao, Miao Xu, Mengting Gou, Bowen Xie, Jinling Huang, Qinli Sun, Lin Sun, Xue Bai, Sangnee Tan, Xiaohu Wang, Chen Dong
Journal: The Journal of Experimental Medicine (2023)

The authors regret that in the originally published Fig. S1 F, two flow images representing CD45.1+ and CD45.2+ILC3
Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study
Authors: Zhiyuan Xu, Yida Huang, Can Hu, Lingbin Du, Yi-An Du, Yanqiang Zhang, Jiangjiang Qin, Wanshan Liu, Ruimin Wang, Shouzhi Yang, Jiao Wu, Jing Cao, Juxiang Zhang, Gui-Ping Chen, Hang Lv, Ping Zhao, Weiyang He, Xiaoliang Wang, Min Xu, Pingfang Wang, Chuanshen Hong, Li-Tao Yang, Jingli Xu, Jiahui Chen, Qing Wei, Ruolan Zhang, Li Yuan, Kun Qian, Xiangdong Cheng
Journal: Gut (2023)

Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead to high-performance blood tests towards GC diagnosis and prognosis. We attempted to develop diagnostic and prognostic models for GC based on plasma metabolic information.We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort and 264 participants in prospective cohort. Discovery and verification phases of diagnostic and prognostic models were conducted in retrospective cohort through machine learning and Cox regression of plasma metabolic fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, the developed diagnostic model was validated in prospective cohort by both NPELDI-MS and ultra-performance liquid chromatography-MS (UPLC-MS).We demonstrated the high throughput, desirable reproducibility and limited centre-specific effects of PMFs obtained through NPELDI-MS. In retrospective cohort, we achieved diagnostic performance with areas under curves (AUCs) of 0.862-0.988 in the discovery (n=1157 from 5 centres) and independent external verification dataset (n=787 from another 2 centres), through 5 different machine learning of PMFs, including neural network, ridge regression, lasso regression, support vector machine and random forest. Further, a metabolic panel consisting of 21 metabolites was constructed and identified for GC diagnosis with AUCs of 0.921-0.971 and 0.907-0.940 in the discovery and verification dataset, respectively. In the prospective study (n=264 from lead centre), both NPELDI-MS and UPLC-MS were applied to detect and validate the metabolic panel, and the diagnostic AUCs were 0.855-0.918 and 0.856-0.916, respectively. Moreover, we constructed a prognosis scoring system for GC in retrospective cohort, which can effectively predict the survival of GC patients.We developed and validated diagnostic and prognostic models for GC, which also contribute to advanced metabolic analysis towards diseases, including but not limited to GC.
Major adverse cardiovascular events and mortality with opioids versus NSAIDs initiation in patients with rheumatoid arthritis
Authors: Gulsen Ozen, Sofia Pedro, Kaleb Michaud
Journal: Annals of the Rheumatic Diseases (2023)

Assess major adverse cardiovascular event (MACE) risk with opioids compared with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA) METHODS: We conducted a new-user active comparator cohort study among patients with RA within FORWARD, The National Databank for Rheumatic Diseases, with ≥1 year participation between 1998 and 2021. Each opioid initiator was matched to two NSAID initiators by propensity scores (PSs). Patients were followed until the occurrence of the composite endpoint of MACE (myocardial infarction, stroke, heart failure, cardiovascular disease (CVD) death, venous thromboembolism (VTE)) and all-cause mortality. The risk of outcomes was estimated using Cox proportional hazards with adjustment for PS weights and imbalanced covariables.Among 6866 opioid initiators and 13 689 NSAID initiators, 212 vs 253 MACE (20.6/1000 person-years (PY) vs 18.9/1000 PY) and 144 vs 150 deaths (13.5/1000 PY vs 10.8/1000 PY) occurred, respectively. The risk of MACE with opioids was similar to NSAIDs (HR=1.02, 95% CI 0.85 to 1.22), whereas all-cause mortality with opioids was 33% higher than NSAIDs (HR=1.33, 95% CI 1.06 to 1.67) in PS-weighted models. Among the individual outcomes of MACE, VTE risk tended to be higher in opioid initiators than NSAID initiators (HR=1.41, 95% CI 0.84 to 2.35). Strong opioids had a higher risk for all-cause mortality and VTE than weak opioids compared with NSAIDs suggesting a dose-dependent association.Opioids had similar MACE risk compared with NSAIDs in patients with RA with increased all-cause mortality and likely VTE, which suggests that opioids are not safer than NSAIDs, as clinicians have perceived.
Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the <scp>SLICC</scp> Inception Cohort
Authors: Yann Nguyen, Benoît Blanchet, Murray B. Urowitz, John G. Hanly, Caroline Gordon, Sang‐Cheol Bae, Juanita Romero‐Diaz, Jorge Sanchez‐Guerrero, Ann E. Clarke, Sasha Bernatsky, Daniel J. Wallace, David A. Isenberg, Anisur Rahman, Joan T. Merrill, Paul R. Fortin, Dafna D. Gladman, Ian N. Bruce, Michelle Petri, Ellen M. Ginzler, Mary Anne Dooley, Rosalind Ramsey‐Goldman, Susan Manzi, Andreas Jönsen, Graciela S. Alarcón, Ronald F. Van Vollenhoven, Cynthia Aranow, Véronique Le Guern, Meggan Mackay, Guillermo Ruiz‐Irastorza, S. Sam Lim, Murat Inanc, Kenneth C. Kalunian, Søren Jacobsen, Christine A. Peschken, Diane L. Kamen, Anca Askanase, Jill Buyon, Nathalie Costedoat‐Chalumeau
Journal: Arthritis & Rheumatology (2023)

Objective The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow‐up. Methods The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level &lt;106 ng/mL or &lt;53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. Results Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39). Conclusion Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five‐year mortality. image
Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway <scp>Co‐Expression</scp> Patterns: A <scp>Double‐Blind</scp>, Randomized, <scp>Placebo‐Controlled</scp>, Phase 2 Trial
Authors: Joan T. Merrill, Joel Guthridge, Miles Smith, Joshua June, Fotios Koumpouras, Wambui Machua, Anca Askanase, Arezou Khosroshahi, Saira Z. Sheikh, Gaurav Rathi, Bart Burington, Paul Foster, Mark Matijevic, Sujata Arora, Xiaodong Wang, Minggeng Gao, Stephen Wax, Judith A. James, Debra J. Zack
Journal: Arthritis & Rheumatology (2023)

Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE).During screening, patients with active, non-organ-threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed). Patients with improved disease activity were randomized 1:1 to obexelimab 5 mg/kg intravenously or placebo once every 2 weeks until week 32 or loss of improvement (LOI).In this study, 104 patients were randomized. Analysis of the primary endpoint, proportion of patients reaching week 32 without LOI, used an efficacy-evaluable (EE) population defined as patients who completed the study or withdrew for flare or treatment-related toxicity. This endpoint did not reach statistical significance: 21 of 50 obexelimab-treated patients (42.0%) versus 12 of 42 patients (28.6%) treated with a placebo (P = 0.183). Time to LOI was increased in obexelimab-treated patients versus patients treated with a placebo in the EE (hazard ratio [HR] 0.53, P = 0.025) and intention-to-treat (HR 0.59, P = 0.062) populations. In obexelimab-treated patients, B cells decreased approximately 50%, and trough concentration and inclusion in baseline gene expression clusters with high B cell pathway modules were associated with increased time to LOI. Obexelimab was associated with infusion reactions but was generally safe and well-tolerated.Although the primary endpoint was not reached, secondary analysis showed time to LOI was significantly increased in obexelimab-treated patients, and analysis of patient subsets defined by gene expression patterns at baseline suggests a responding subpopulation.
Robust estimation of cortical similarity networks from brain MRI
Authors: Isaac Sebenius, Jakob Seidlitz, Varun Warrier, Richard A. I. Bethlehem, Aaron Alexander-Bloch, Travis T. Mallard, Rafael Romero Garcia, Edward T. Bullmore, Sarah E. Morgan
Journal: Nature Neuroscience (2023)

Abstract Structural similarity is a growing focus for magnetic resonance imaging (MRI) of connectomes. Here we propose Morphometric INverse Divergence (MIND), a new method to estimate within-subject similarity between cortical areas based on the divergence between their multivariate distributions of multiple MRI features. Compared to the prior approach of morphometric similarity networks (MSNs) on n &gt; 11,000 scans spanning three human datasets and one macaque dataset, MIND networks were more reliable, more consistent with cortical cytoarchitectonics and symmetry and more correlated with tract-tracing measures of axonal connectivity. MIND networks derived from human T1-weighted MRI were more sensitive to age-related changes than MSNs or networks derived by tractography of diffusion-weighted MRI. Gene co-expression between cortical areas was more strongly coupled to MIND networks than to MSNs or tractography. MIND network phenotypes were also more heritable, especially edges between structurally differentiated areas. MIND network analysis provides a biologically validated lens for cortical connectomics using readily available MRI data.
Identification of ligand–receptor pairs that drive human astrocyte development
Authors: Anna J. Voss, Samantha N. Lanjewar, Maureen M. Sampson, Alexia King, Emily J. Hill, Anson Sing, Caitlin Sojka, Tarun N. Bhatia, Jennifer M. Spangle, Steven A. Sloan
Journal: Nature Neuroscience (2023)
Siglec-9 acts as an immune-checkpoint molecule on macrophages in glioblastoma, restricting T-cell priming and immunotherapy response
Authors: Yan Mei, Xiumei Wang, Ji Zhang, Dan Liu, Junjie He, Chunliu Huang, Jing Liao, Yingzhao Wang, Yongyi Feng, Hongyu Li, Xiuying Liu, Lingdan Chen, Wei Yi, Xi Chen, Hong-Min Bai, Xinyu Wang, Yiyi Li, Lixiang Wang, Zhigang Liang, Xianwen Ren, Li Qiu, Yuan Hui, Qingling Zhang, Qibin Leng, Jun Chen, Guangshuai Jia
Journal: Nature Cancer (2023)